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THE SIGNIFICANCE OF CHROMOSOMAL TRANSLOCATION INVOLVING BCL6 GENE IN MALIGNANT LYMPHOMA

BCL6基因染色体易位在恶性淋巴瘤中的意义

基本信息

批准号：
12670977
负责人：
MIKI Tohru
金额：
$ 2.18万
依托单位：
TOKYO MEDEICAL AND DENTAL UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670977/
关键词：
Malignant Lymphoma BCL6 Chromosomal translocation BAZF

项目摘要

We identified two regions in the BCL6 gene that negatively regulate BCL6 expression. One region, ES, is located within the first and a second region, IS, is located within the first intron. A consensus nucleotide sequence for the binding of the BCL6 protein itself was found within the ES. The IS region which is included in the regions commonly deleted in B-cell lymphomas had a silencer activity. Structural alterations of these two regions may play roles in the deregulated expression of the BCL6 gene in B-cell lymphomas.We report a case of non-Hodgkin's lymphoma of unknown origin with invasion into bone marrow and brain. Using FISH and SKY technique, we identified the new partner site of the 14q32 translocation, 22q13, and the jumping translocations involving 2p23 as a new donor chromosome. We could also identify the unbalanced translocation of t(3 ; 14)(q27 ; q32). The combination of SKY and FISH using the 14q telomere probe was therefore considered very useful for the characterization of complex cytogenetic cases in B-cell lymphoma.We cloned the human BAZF gene, homologue of protooncogene BCL6, using murine BAZF as a probe. The predicted amino acid sequence was 91% identical to that of murine BAZF. Fluorescence in situ hybridization analysis revealed that the human BAZF gene is located on chromosome 17p13.1. Although expression of human BAZF mRNA was ubiquitously detected in human tissues, abundant expression was detected in heart and placenta. BAZF mRNA was expressed in some immature B cell lines and erythroleukemia cell lines. The expression in a human erythroleukemia cell line, HEL cells, was upregulated during megakaryocytic differentiation induced by TPA.

我们确定了BCL 6基因中负调控BCL 6表达的两个区域。一个区域ES位于第一内含子内，第二区域IS位于第一内含子内。在ES内发现了用于BCL 6蛋白本身结合的共有核苷酸序列。B细胞淋巴瘤中通常缺失的区域中包含的IS区域具有沉默活性。这两个区域的结构改变可能在BCL 6基因在B细胞淋巴瘤中的表达失调中发挥作用。我们报告一例起源不明的非霍奇金淋巴瘤，侵犯骨髓和脑。我们用FISH和SKY技术鉴定了14 q32易位的新伴侣位点22 q13和涉及2 p23的跳跃易位为新的供体染色体。我们还发现了t（3 ; 14）（q27 ; q32）的不平衡易位。因此，SKY和FISH的组合使用的14 q端粒探针被认为是非常有用的复杂的细胞遗传学的情况下，在B细胞lymphoma.We克隆人BAZF基因，同源的原癌基因BCL 6，使用小鼠BAZF作为探针。预测的氨基酸序列与小鼠BAZF的氨基酸序列有91%的相同性。荧光原位杂交分析表明，人BAZF基因位于染色体17p13.1。虽然人BAZF mRNA在人体组织中广泛表达，但在心脏和胎盘中检测到大量表达。BAZF mRNA在部分未成熟B细胞系和红白血病细胞系中表达。在TPA诱导的人红白血病细胞系HEL细胞巨核细胞分化过程中，其表达上调。